Significantly inhibitory effects of low molecular weight heparin (Fraxiparine) on the motility of lung cancer cells and its related mechanism

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• 作者：Guo-xing Zhong ; Yi Gong ; Chuan-jiang Yu ; Shi-fei Wu ; Qing-ping Ma ; Yu Wang…
• 关键词：Fraxiparine ; Lung cancer ; Actin cytoskeleton ; Motility ; PI3K ; Akt ; mTOR ; CXCL12 ; CXCR4 axis
• 刊名：Tumor Biology
• 出版年：2015
• 出版时间：June 2015
• 年：2015
• 卷：36
• 期：6
• 页码：4689-4697
• 全文大小：2,953 KB
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  22.Xing X, Zhang L,
• 作者单位：Guo-xing Zhong (1) (2)
  Yi Gong (1)
  Chuan-jiang Yu (1)
  Shi-fei Wu (1)
  Qing-ping Ma (1)
  Yu Wang (1)
  Jiang Ren (1)
  Xue-chao Zhang (1)
  Wei-han Yang (1)
  Wen Zhu (1)
  
  1. State Key Laboratory of Biotherapy, West China Hospital, Sichuan University, Chengdu, 610041, China
  2. Central Laboratory, Shenzhen Baoan Maternal and Child Health Hospital, Shenzhen, 518133, China
  
• 刊物主题：Cancer Research;
• 出版者：Springer Netherlands
• ISSN：1423-0380

文摘

Low molecular weight heparin (LMWH) improving the cancer survival has been attracting attention for many years. Our previous study found that LMWH (Fraxiparine) strongly downregulated the invasive, migratory, and adhesive ability of human lung adenocarcinoma A549 cells. Here, we aimed to further identify the antitumor effects and possible mechanisms of Fraxiparine on A549 cells and human highly metastatic lung cancer 95D cells. The ability of cell invasion, migration, and adhesion were measured by Transwell, Millicell, and MTT assays. FITC-labeled phalloidin was used to detect F-actin bundles in cells. Chemotactic migration was analyzed in a modified Transwell assay. Measurement of protein expression and phosphorylation activity of PI3K, Akt, and mTOR was performed with Western blot. Our studies found that Fraxiparine significantly inhibited the invasive, migratory, and adhesive characteristics of A549 and 95D cells after 24?h incubation and showed a dose-dependent manner. Fraxiparine influenced the actin cytoskeleton rearrangement of A549 and 95D cells by preventing F-actin polymerization. Moreover, Fraxiparine could significantly inhibit CXCL12-mediated chemotactic migration of A549 and 95D cells in a concentration-dependent manner. Furthermore, Fraxiparine might destroy the interaction between CXCL12-CXCR4 axis, then suppress the PI3K-Akt-mTOR signaling pathway in lung cancer cells. For the first time, our data indicated that Fraxiparine could significantly inhibit the motility of lung cancer cells by restraining the actin cytoskeleton reorganization, and its related mechanism might be through inhibiting PI3K-Akt-mTOR signaling pathway mediated by CXCL12-CXCR4 axis. Therefore, Fraxiparine would be a potential drug for lung cancer metastasis therapy.